Comparative anti-fracture effectiveness of different oral anti-osteoporosis therapies based on "real-world" data: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database

Sara Khalid, Sara Calderon-Larranaga, Sam Hawley, M Sanni Ali, Andrew Judge, Nigel Arden, Tjeerd Van Staa, Cyrus Cooper, Muhammad Kassim Javaid, Daniel Prieto-Alhambra

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Purpose: To compare the clinical effectiveness of oral anti-osteoporosis drugs based on the observed risk of fracture while on treatment in primary care actual practice.

Patients and methods: We investigated two primary care records databases covering UK NHS (CPRD) and Catalan healthcare (SIDIAP) patients during 1995-2014 and 2006-2014 respectively. Treatment naive incident users of anti-osteoporosis drugs were included and followed until treatment cessation, switching, death, transfer out, or study completion. We considered hip fracture while on treatment as main outcome, and major osteoporotic fractures (hip, clinical spine, wrist, and proximal humerus) as secondary outcome. Users of alendronate (reference group) were compared to those of 1. other oral bisphosphonates (OBP), 2. stron-tium ranelate (SR), and 3. selective estrogen receptor modulators (SERMs), after matching on baseline characteristics using propensity scores. Multiple imputation was used to handle missing data on confound-ers, and competing risk modelling for the calculation of relative risk according to therapy. Country-specific data were analysed separately and meta-analysed.

Results: 163,950 UK and 145,236 Catalan patients were identified. Hip (SHR [95% CI] 1.04 [0.77 - 1.40]) and major osteoporotic (SHR [95% CI] 1 [0.78 - 1.27]) fracture risks were similar amongst OBP compared to alendronate users. Both hip (SHR [95% CI] 1.26 [1.14 - 1.39]) and major osteoporotic (SHR [95% CI] 1.06 [1.02 - 1.12]) fracture risk were higher in SR compared to alendronate users. SERM users had a reduced hip (SHR [95% CI] 0.75 [0.60 - 0.94]) and major osteoporotic (SHR [95% CI] 0.77 [0.72 - 0.83]) fracture risk compared to alendronate users.

Conclusion: We found a 26% excess hip fracture risk among SR compared to matched alendronate users, in line with placebo-controlled RCT findings. Conversely, in a lower risk population, SERM users had a 25% reduced hip fracture risk compared to alendronate users. Head-to-head RCTs are needed to confirm these findings.
Original languageEnglish
Pages (from-to)1417-1431
Number of pages15
JournalJournal of Clinical Epidemiology
Volume10
Early online date5 Oct 2018
DOIs
Publication statusPublished - Oct 2018

Keywords

  • pharmaco-epidemiology
  • anti-osteoporosis medication
  • osteoporosis
  • fracture risk
  • electronic health records

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